Combined functions of two RRMs in Dead-end1 mimic helicase activity to promote nanos1 translation in the germline

Mol Reprod Dev. 2018 Dec;85(12):896-908. doi: 10.1002/mrd.23062. Epub 2018 Oct 18.

Abstract

Dead-end1 (Dnd1) expression is restricted to the vertebrate germline where it is believed to activate translation of messenger RNAs (mRNAs) required to protect and promote that unique lineage. Nanos1 is one such germline mRNA whose translation is blocked by a secondary mRNA structure within the open reading frame (ORF). Dnd1 contains a canonical RNA recognition motif (RRM1) in its N-terminus but also contains a less conserved RRM2. Here we provide a mechanistic picture of the nanos1 mRNA-Dnd1 interaction in the Xenopus germline. We show that RRM1, but not RRM2, is required for binding nanos1. Similar to the zebrafish homolog, Xenopus Dnd1 possesses ATPase activity. Surprisingly, this activity appears to be within the RRM2, different from the C-terminal region where it is found in zebrafish. More importantly, we show that RRM2 is required for nanos1 translation and germline survival. Further, Dnd1 functions as a homodimer and binds nanos1 mRNA just downstream of the secondary structure required for nanos1 repression. We propose a model in which the RRM1 is required to bind nanos1 mRNA while the RRM2 is required to promote translation through the action of ATPase. Dnd1 appears to use RRMs to mimic the function of helicases.

Keywords: Dead-end1; Xenopus; germline development; nanos1; translational regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Models, Biological*
  • Protein Biosynthesis*
  • Protein Domains
  • RNA Helicases* / chemistry
  • RNA Helicases* / genetics
  • RNA Helicases* / metabolism
  • RNA Recognition Motif
  • RNA, Messenger* / chemistry
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA-Binding Proteins* / chemistry
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Repressor Proteins* / biosynthesis
  • Repressor Proteins* / chemistry
  • Repressor Proteins* / genetics
  • Xenopus Proteins* / biosynthesis
  • Xenopus Proteins* / chemistry
  • Xenopus Proteins* / genetics
  • Xenopus Proteins* / metabolism
  • Xenopus laevis

Substances

  • Dnd1 protein, Xenopus
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • Xenopus Proteins
  • nanos1 protein, Xenopus
  • RNA Helicases